Volatile organic compound exposure in relation to lung cancer: Insights into mechanisms of action through metabolomics

Volatile organic compounds (VOCs) have proven to be hazardous to the human respiratory system. However, the underlying biological mechanisms remain poorly understood. Therefore, targeted determination of eleven VOC metabolites (mVOCs) along with the nontargeted metabolomic analysis was performed on urine samples collected from lung cancer patients and healthy individuals. Nine mVOCs mainly derived from aldehydes, alkenes, amides, and aromatics were detected in > 90 % of the urine samples, suggesting that the participants were ubiquitously exposed to these typical VOCs. A molecular gatekeeper discovery workflow was employed to link the exposure biomarkers with correlated clusters of endogenous metabolites. As a result, multiple metabolic pathways, including amino acid metabolism, steroid hormone biosynthesis and metabolism, and fatty acid β -oxidation were connected with VOC exposure. Furthermore, 16 of 73 molecular gatekeepers were associated with lung cancer and pointed to a few disrupted metabolic pathways related to hydroxysteroids and acylcarnitine. The shift in molecular profiles was validated in rat model post VOC administration. Thereinto, the up-regulation of enzymes involved in acylcarnitine synthesis and transport in rat lung tissues highlighted that the mitochondrial dysfunction may be a potential carcinogenic mechanism. Our findings provide new insights into the mechanisms underlying lung cancer induced by VOC exposure.